Carboplatin, Paclitaxel, and Bevacizumab With or Without Everolimus in Treating Patients With Metastatic Malignant Melanoma
|Melanoma (Skin)||Biological: bevacizumab Drug: carboplatin Drug: everolimus Drug: paclitaxel||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Randomized Phase II Trial of Carboplatin, Paclitaxel, Bevacizumab, With or Without Everolimus for Therapy of Metastatic Malignant Melanoma|
- Progression-free Survival [ Time Frame: Time from randomization to documentation of disease progression or death without documentation of progression;Up to 5 years ]The primary endpoint is progression-free survival (PFS) defined as the time from randomization to documentation of disease progression or death without documentation of progression. The distribution of PFS times will be estimated using the Kaplan-Meier method. Progression is defined using the RECIST Criteria as at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum of diameters recorded on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm of target lesions, or the appearance of one or more new lesions, unequivocal progression of existing non-target lesions, although unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
- Toxicity [ Time Frame: Up to 5 years ]For this secondary endpoint, toxicity is defined as a grade 3 or higher adverse events that is classified as either possibly, probably, or definitely related to study treatment. The assignment of attribution to study treatment and grade (or degree of severity) of the adverse event are classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The percentage of participants reporting a grade 3 or higher toxicity is reported. For a list of all reported adverse events, please refer to the Adverse Events Section below.
- Confirmed Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria [ Time Frame: Up to 5 years ]Confirmed Tumor Response: A confirmed tumor response is defined to be a CR or PR (by the RECIST criteria) noted as the objective status on 2 consecutive evaluations at least 8 weeks apart. The proportion of tumor responses will be estimated by the number of confirmed tumor responses divided by the total number of evaluable patients. A ninety percent confidence interval for the true proportion of confirmed tumor responses will be calculated assuming that the number of confirmed tumor responses follows a binomial distribution.
- Overall Survival Time [ Time Frame: up to 5 years ]Overall survival time is defined as the time from registration to death due to any cause. The distribution of survival times will be estimated using the method of Kaplan-Meier.
|Study Start Date:||April 2010|
|Study Completion Date:||September 2015|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm I (bevacizumab, paclitaxel, and carboplatin)
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Given IVDrug: carboplatin
Given IVDrug: paclitaxel
Experimental: Arm II(bevacizumab, paclitaxel, carboplatin, and everolimus)
Patients receive bevacizumab, paclitaxel, and carboplatin as in Arm I. Patients also receive everolimus PO QD on 3 days a week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Given IVDrug: carboplatin
Given IVDrug: everolimus
Given orallyDrug: paclitaxel
- To assess whether there is sufficient promise of an impact of the addition of everolimus to the combination of carboplatin, paclitaxel, and bevacizumab on progression-free survival that it would be recommended for further testing in patients with metastatic malignant melanoma.
- To estimate the confirmed tumor response rate of each of the treatment regimens.
- To estimate the distribution of overall survival (OS) time for each of the treatment regimens.
- To assess the impact on the safety profile of the addition of everolimus to the combination of carboplatin, paclitaxel, and bevacizumab.
OUTLINE: This is a multicenter study. Patients are stratified according to elevated LDH (above upper limit of normal) at baseline (yes vs no), location of metastatic disease (M1a [skin, subcutaneous tissue, or lymph node only] vs M1b [lung] vs M1c [other visceral sites]) and prior chemotherapy for metastatic disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive bevacizumab, paclitaxel, and carboplatin as in Arm I. Patients also receive everolimus orally (PO) once daily (QD) 3 times weekly. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3-6 months for up to 5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00976573
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|Study Chair:||Robert McWilliams, MD||Mayo Clinic|